New findings from an RV144 follow-on study published today in Science Translational Medicine provide key insights into the role that host-genetics played in protecting against HIV-1 infection during the landmark “Thai Study.”
Researchers at the U.S. Military HIV Research Program (MHRP) tested whether specific variants of immune response genes called HLA were associated with greater protection against the virus.
“We found that antibody responses correlated with increased or decreased risk of acquiring HIV only in the presence of specific host HLA alleles,” said senior author Dr. Rasmi Thomas. By identifying this specific allele, or gene variation, researchers hope to more clearly determine the mechanism of protection.
Led by the US Army, the RV144 trial is the only HIV vaccine trial to show efficacy in preventing HIV-1 infection over the course of 42 months. Since researchers can compare data from those protected against HIV to those who were not, RV144 follow-on studies have advanced the understanding of HIV vaccine-induced protective immune responses. Two immune correlates of risk were identified previously, and subsequent studies have analyzed both viral and host genetics for further insights into how the vaccine worked.
HLA class II molecules play an important role in antibody response, so MHRP researchers tested variation in these genes for interactions with the two vaccine-induced correlates of risk identified in RV144. This study showed that particular HLA class II genes modulated the quantity and quality of vaccine-induced antibody responses to affect HIV acquisition and vaccine efficacy.